Molecular Biology Reports最新文献

Background: Endometriosis (EMs) is a chronic enigmatic gynecological disorder which pathogenesis have not been fully elucidated. Exosomes have been proven to participate in endometriosis. However, the role of exosomes in the pathogenesis of EMs remains poorly defined.

Methods: Exosomes were isolated from cyst fluid of EMs patients and pelvic fluid of non-EMs patients, and characterized by transmission electron microscopy, nanoparticle tracking analysis and western blot. Exosomal miRNAs were performed by small RNA sequencing. Q-PCR and cell function were performed to identify the relationship between exosomal miRNAs and endometriosis. Dual luciferase reporter assay, cell transfection, Q-PCR, Western blotting and CCK8 assays, Transwell assays and Boyden assays were conducted to explore the regulatory effects of exosomal miRNA on EMs pathogenesis in vitro using primary human endometrial stromal cells (HESCs) derived from endometriotic lesions.

Results: Compare with non-EMs group, there are 118 miRNAs were up-regulated and 40 miRNAs were down-regulated in CF group, meanwhile 22 miRNAs were up-regulated and 32 miRNAs were down-regulated in PF group. Q-PCR verified that miR-125b-5p, miR-328-3p, miR-125a-5p, miR-30e-3p were significant down-regulated, whereas miR-3141, miR-223-3p, miR-142-5p, miR-1246 were significant up-regulated in EMs patients. ROC analysis indicated that miR-125b-5p (AUC = 0.925, p < 0.001) was highly correlated with EMs pathogenesis. Dual luciferase reporter assay results demonstrated miR-125b-5p directly targeted VEGF gene. MiR-125b-5p suppressed endometrial stromal cells proliferation, migration and invasion by regulating the Phosphatidylinositol 3-Kinase (PI3K) /Protein Kinase B (AKT) signaling pathway.

Conclusion: Exosomal miR-125b-5p was highly correlated with EMs, and it regulates the PI3K/Akt signaling pathways through VEGF to inhibit endometrial stromal cells proliferation, migration and invasion, acting as an important suppressing miRNA in endometriosis pathogenesis.

Background: Patients undergoing cardiac surgery frequently suffer impaired myocardial redox protection during cardiopulmonary bypass (CPB), with elderly patients facing higher complication risks. We investigated the redox-protective effects of blood versus del Nido cardioplegia on systemic redox homeostasis, stratified by age, in patients undergoing coronary bypass and isolated valve surgery.

Methods: Systemic redox biomarkers were assessed with immunochemical and spectrophotometric methods in patients stratified by cardioplegia type (blood vs. del Nido) and age (< 60 vs. ≥60 years). Redox biomarkers such as MnSOD, catalase, total thiol, PCO, AOPP, LOOH, GPxA, and AGE were analyzed in blood samples of postoperative CPB patients (n = 60).

Results: MnSOD levels were significantly higher with blood cardioplegia, indicating increased mitochondrial oxidative stress, whereas lower levels in the del Nido group suggested improved redox balance. Catalase activity appeared higher in the del Nido group, potentially influenced by outliers. Total thiol levels varied significantly among younger patients: those receiving blood cardioplegia had higher thiol concentrations, suggesting a more robust antioxidant buffer. No significant differences were observed regarding PCO, AOPP, LOOH, GPxA, or AGE between groups.

Conclusions: This analysis highlights MnSOD as the most reliable biomarker for differentiating cardioplegia strategies. Lower MnSOD levels in the del Nido group support its superior redox-protective effects, which are particularly relevant for reducing surgical complications in elderly patients undergoing cardiac surgery.

The incorporation of organoids with immune cells in co-culture systems signifies a groundbreaking advancement in the fields of cancer research and immunology. These three-dimensional models, derived from primary tumor specimens or stem cells, provide a more accurate representation of the tumor microenvironment (TME) than conventional two-dimensional cultures or animal models. This enhanced model allows for a thorough examination of the intricate interactions between cancer cells and the immune system. Although the success rates for organoid initiation can vary, averaging 36.8% across 13 different tumor types, successful organoid establishment enables the co-culture with a variety of immune cells, such as T cells, tumor-infiltrating lymphocytes (TILs), peripheral blood mononuclear cells (PBMCs), macrophages, dendritic cells, and natural killer (NK) cells. This platform enables the study of immune responses to cancer, mechanisms of immune evasion, and the influence of the TME on immune activation and suppression. The review emphasizes research involving intestinal, pancreatic, brain, liver, and cervical organoids, highlighting their role in elucidating disease mechanisms, assessing the effectiveness of immunotherapies (including checkpoint inhibitors and therapeutic vaccines), and conducting preclinical drug evaluations. Notable examples include modeling graft-versus-host disease with intestinal organoids, investigating the influence of DCLK1 on immunosuppression in pancreatic cancer, evaluating the effectiveness of engineered T cells against neuroblastoma using brain organoids, and analyzing the effects of cancer-associated fibroblasts on drug responses in colon cancer. Additionally, the potential of organoids in vaccine development and testing, particularly for influenza and other viral infections, is examined, demonstrating their utility in assessing immune responses and vaccine effectiveness. Despite existing challenges, such as the relatively low efficiency of organoid generation and the complexities involved in fully mimicking the TME, ongoing technological innovations, including tumor-on-chip systems and enhanced matrix materials, are expected to improve the functionality and clinical applicability of these advanced in vitro models.